Marijuana dependence is a significant problem in the United States today. It is critical to expand the investigation of treatment options for patients with marijuana use disorders. Attention deficit hyperactivity disorder (ADHD) commonly co-occurs in patients with marijuana use disorders, and comorbid substance use disorders have been shown to worsen treatment outcomes. Dopamine dysfunction is a hypothesized link between ADHD and substance use disorders, and it has been postulated that illicit substances may be used by individuals with ADHD to overcome a relative lack of dopamine transmission. Preliminary studies suggest that the use of medications that increase dopaminergic levels may improve substance use outcomes in these patients. The first-line treatment of ADHD is stimulant medications. However, there has been concern about the use of stimulants in individuals with substance use disorders because of the abuse potential of these agents. This R21 application proposes to explore the treatment of adult patients with comorbid marijuana dependence and ADHD with atomoxetine, a recently approved non-stimulant ADHD medication. Subjects will receive treatment with either atomoxetine or placebo for 12 weeks combined with brief motivational enhancement therapy. Measures of marijuana use and craving and ADHD symptomatology will be collected. The specific aims of this project are to gather preliminary data on the safety and efficacy of atomoxetine in reducing marijuana use in adult patients with comorbid ADHD and marijuana dependence, and to preliminarily evaluate the efficacy of atomoxetine in reducing ADHD symptoms in this population. The proposed work is novel in that little clinical research has focused on marijuana-dependent patients with ADHD, and no work has been published examining the safety, tolerability, or efficacy of atomoxetine inpatients with this comorbidity. The project is designed to increase our knowledge of treatment options for patients with marijuana dependence, an area which has been under investigated. [unreadable] [unreadable]